Agreement covers Phase I small molecule glucokinase activator and second-generation products.
Amgen is putting down $60 million for Array BioPharma’s small molecule glucokinase activator program. The deal grants Amgen exclusive, worldwide rights to ARRY-403, currently in Phase I for type 2 diabetes, and additional back-up candidates.
Array is responsible for completing the Phase I trial for ARRY-403. Additionally, Amgen will fund an agreed upon number of full-time Array employees as part of a two-year research collaboration intended to identify and advance second-generation glucokinase activators.
Amgen will take over clinical development of back-up compounds as well as ARRY-403 after Phase I is completed. It is also responsible for final commercialization of all products resulting from this partnership. Array retains an option to co-promote in the U.S. and will receive double-digit royalties on sales of ARRY-403.
In normal individuals, the pancreas secretes insulin in response to increased levels of glucose in the blood. Glucokinase (GK) is the enzyme that senses glucose in the pancreas. GK also increases glucose utilization and decreases glucose production in the liver.
In patients with type 2 diabetes there is a reduction of GK activity in the pancreas and the liver. This results in its inability to sense the level of glucose in the pancreas as well as decreased glucose utilization and production. Activating GK lowers blood glucose levels by enhancing the ability of the pancreas to sense glucose, which leads to increased insulin production. Simultaneously, glucokinase activators increase the net uptake of blood glucose by the liver, the companies report.
ARRY-403 is a potent, selective, and orally administered small molecule glucokinase activator. It demonstrated dose-dependent glucose reductions in a Phase I single ascending-dose study.
Amgen has three antidiabetic candidates in the clinic. Darbepoetin alfa, a recombinant protein agonist of the erythropoietin receptor, is the most advanced in Phase III. AMG 222, an orally administered small molecule antagonist of DPP-IV, is being investigated in Phase II. The compound is being developed in partnership with Servier. In Phase I is AMG 221, an orally administered small molecule antagonist of 11-beta hydroxysteroid dehydrogenase type 1, an enzyme associated with conversion of cortisone to cortisol in the liver and adipose tissue.